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Escolano, Amelia; Gristick, Harry B; Abernathy, Morgan E; Merkenschlager, Julia; Gautam, Rajeev; Oliveira, Thiago Y; Pai, Joy; West, Jr, Anthony P; Barnes, Christopher O; Cohen, Alexander A; Wang, Haoqing; Golijanin, Jovana; Yost, Daniel; Keeffe, Jennifer R; Wang, Zijun; Zhao, Peng; Yao, Kai-Hui; Bauer, Jens; Nogueira, Lilian; Gao, Han; Voll, Alisa V; Montefiori, David C; Seaman, Michael S; Gazumyan, Anna; Silva, Murillo; McGuire, Andrew T; Stamatatos, Leonidas; Irvine, Darrell J; Wells, Lance; Martin, Malcolm A; Bjorkman, Pamela J; Nussenzweig, Michel C
Nature (London), 06/2019, Volume: 570, Issue: 7762Journal Article
Broadly neutralizing monoclonal antibodies protect against infection with HIV-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. However, it has not yet been possible to induce adequate serological responses by vaccination. Here, to activate B cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, RC1, that facilitates the recognition of the variable loop 3 (V3)-glycan patch on the envelope protein of HIV-1. RC1 conceals non-conserved immunodominant regions by the addition of glycans and/or multimerization on virus-like particles. Immunization of mice, rabbits and rhesus macaques with RC1 elicited serological responses that targeted the V3-glycan patch. Antibody cloning and cryo-electron microscopy structures of antibody-envelope complexes confirmed that immunization with RC1 expands clones of B cells that carry the anti-V3-glycan patch antibodies, which resemble precursors of human broadly neutralizing antibodies. Thus, RC1 may be a suitable priming immunogen for sequential vaccination strategies in the context of polyclonal repertoires.
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